To assess male fertility, doctors stain sperm (shown) and look for visual signs of dysfunction, such as low count and poor motility. Yet sperm that pass these tests can still fail to fertilize an egg, leaving researchers searching for better diagnostic methods.

Credit: Bobjgalindo/Wikimedia Commons

Fertile Or Not?

To assess male fertility, doctors stain sperm (shown) and look for visual signs of dysfunction, such as low count and poor motility. Yet sperm that pass these tests can still fail to fertilize an egg, leaving researchers searching for better diagnostic methods.

Credit: Bobjgalindo/Wikimedia Commons

For some men who struggle with fertility issues, doctors have a frustrating lack of answers. These men’s sperm cells pass all the standard medical tests for fertility, however they are infertile—a condition called normozoospermic infertility. Now, researchers report that the levels of five small molecules in urine can discriminate between fertile men and those with this condition (J. Proteome Res. 2014, DOI: 10.1021/pr5003142). The molecular signature could be used to develop an alternative fertility screen, as well as help doctors better understand the mechanism of this kind of infertility.

Men are responsible for about 60% of the cases of infertility among couples. For men with normozoospermic infertility, there are no clear clinical indicators, such as low sperm count or poor sperm motility. So Francis L. Martin of Lancaster University, in the U.K., and Heqing Shen of the Chinese Academy of Sciences wanted to develop a simple means to diagnose this form of infertility by looking for biomarkers in patients’ urine.

The researchers collected urine samples from 47 fertile men and 71 infertile men whose semen quality was indistinguishable according to the standard tests. The team analyzed the urine samples with mass spectrometry and picked out those chemicals that had significantly different concentrations between the two groups of men, identifying 37 potential biomarkers. Next, they narrowed the field to only those biomarkers best able to distinguish the two groups according to a statistical model. The analysis pointed to five chemicals: leukotriene E4, 3-hydroxypalmitoylcarnitine, aspartate, xanthosine, and methoxytryptophan. The relative concentrations of these five in a urine sample allowed the researchers to correctly identify 86% of the infertile men and 87% of the fertile men. “That is quite high,” Martin says, as standard fertility tests may capture only 75% of cases.

The biomarkers suggested physiological problems that may contribute to normozoospermic infertility, including dysfunctional energy production and oxidative stress in sperm-producing tissues. For example, making sperm is an energy-intensive process for the body, so any hiccup in a cell’s energy-generating pathways could disrupt proper sperm production. Meanwhile, lifestyle factors such as poor diet and lack of exercise could increase oxidative stress in testicular tissues, causing damage to sperm that is not apparent in standard diagnostic tests, Martin says.

“This is a patient group for which we don’t have much of a way to tell that they’re infertile,” so there is a huge need for new fertility tests, says Dolores J. Lamb of the Baylor College of Medicine. While the results are promising, this is only the first step, she says, as larger studies are needed to confirm the findings. Martin agrees, saying they’re currently working on a study with more participants